Vertebrate embryo immune systems any common features at various levels of biological organization: genetic, cellular and physiologic. Our long term interests are centered upon: (i) describing sites of generation of embryonic B and T lymphocytes, (ii) assessing possible unique structural/functional features associated with lymphocytes derived from these sites, and (iii) understanding how endogenous and exogenous factors may influence development and deployment of lymphocytes in vertebrate embryogenesis. Recent studies indicate that a large portion of lymphocytes (greater than 20%) in mouse and human embryos are highly interactive with one another. This autoreactivity (connectivity) is based upon autoantiidiotype/idiotype interactions. In mice, cells in this interconnected self-referential nonconventional embryonic immune system network (CIS) bear the Ly-1 antigen on their surfaces, whilst lymphocytes belonging to the human embryo CIS express the Ly-1 homolog - CD5. Interactions of CIS lymphocytes results in a networked immune system which is self-referential. Thus, CIS lymphocytes are not dependent upon external antigenic stimulation for their expansion as are antigen-dependent lymphocytes of the conventional immune system. Lymphocytes belonging to the CIS appear to be the first lymphocytes formed and their V region sequences appear to be directly encoded in the germline. This appears to genetically guarantee the vertebrate embryo a self-referential immune system. Recently, it has been suggested that self-stimulating, self-maintaining B cells of CIS are the source of normal immunoglobulin (Ig), especially IgM, found in normal embryonic and adult serum. Evidence suggests that certain autoimmune disorders may represent situations where the CIS network has been detrimentally- altered. Consistent with this perspective, treatment of patients with therapeutic doses of normal Ig helped to alleviate their disease symptoms. Experiments outlined herein are designed: (i) to use modern immunofluorescent microscopy methods to assess the effects of treatment with Ig, primarily IgM, on the development of B and T cells in chicken embryos, (ii) to use ELISA techniques in order to assess the effects of Ig on serum Ig levels in embryos, and (iii) to conduct a pilot study in order to assess the effects of Ig on adult chickens with symptoms of autoimmune disease.